Research published in Journal of Medicinal Chemistry

Modified ibogaine fragments: synthesis and preliminary pharmacological characterization of 3-ethyl-5-phenyl-1,2,3,4,5, 6-hexahydroazepino[4,5-b]benzothiophenes.

Journal of Medicinal Chemistry November 5, 1998 Simon M. N. Efange, Deborah C. Mash, A B Khare et al. 33 citations

Five phenyl-substituted derivatives and analogues of 1,2,3,4,5, 6-hexahydroazepino[4,5-b]indole, 5, a major fragment of ibogaine (1), were synthesized and tested for binding to monoamine transporters, the NMDA receptor-coupled cation channel, and dopamine and opioid receptors. All five derivatives, 9 and 17a-d, displayed 8-10-fold higher affinity at the DA transporter than ibogaine and...

DOI: 10.1021/jm980156y Full text Drug discovery New compounds Novel compounds Synthesized +18

Substituted Naphthofurans as Hallucinogenic Phenethylamine−Ergoline Hybrid Molecules with Unexpected Muscarinic Antagonist Activity

Journal of Medicinal Chemistry May 1, 1998 Aaron Monte, Danuta Marona‐lewicka, Mechelle M. Lewis et al. 20 citations

A series of substituted racemic naphthofurans were synthesized as "hybrid" molecules of the two major prototypical hallucinogenic drug classes, the phenethylamines and the tryptamines/ergolines. Although it was hypothesized that these new agents might possess high affinity for the serotonin 5-HT2A/2C receptor subtypes, unexpected affinity for muscarinic receptors was observed. The compounds...

DOI: 10.1021/jm980076u Serotonin Phenethylamines Muscarinic acetylcholine receptor Stereochemistry +7

Synthesis and Pharmacological Evaluation of Ring-Methylated Derivatives of 3,4-(Methylenedioxy)amphetamine (MDA)

Journal of Medicinal Chemistry February 24, 1998 Matthew Parker, Danuta Marona‐lewicka, Deborah M. Kurrasch et al. 25 citations

The three isomeric ring-methylated derivatives of the well-known hallucinogen and entactogen MDA (1a) were synthesized and evaluated for pharmacological activity as monoamine-releasing agents and as serotonin agonists. The 2-methyl derivative 2a and the 5-methyl derivative 2b were found to be more potent and more selective than the parent compound in inhibiting [3H]-serotonin accumulation in...

DOI: 10.1021/jm9705925 Serotonin Methylenedioxy Pharmacology Hallucinogen +11

Dihydrobenzofuran Analogues of Hallucinogens. 4. Mescaline Derivatives

Journal of Medicinal Chemistry September 1, 1997 Aaron Monte, Steve R. Waldman, Danuta Marona‐lewicka et al. 89 citations

Dihydrobenzofuran and tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in the prototypical hallucinogen, mescaline (1). Thus, 4-(2-aminoethyl)-6,7-dimethoxy-2,3-dihydrobenzofuran hydrochloride (8) and 1-(8-methoxy-2,3,5,6-tetrahydrobenzo[1,2-b:5,4-b']difuran-4-yl)-2- aminoethane hydrochloride (9) were prepared and...

DOI: 10.1021/jm970219x Mescaline Serotonin Lysergic acid diethylamide Pharmacology +12

Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups

Journal of Medicinal Chemistry 1996 Aaron Monte, Danuta Marona‐lewicka, Matthew Parker et al. 106 citations

Tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in prototypical hallucinogenic phenylalkylamines 1 and 2. Thus, a series of 8-substituted 1-(2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)-2-aminoal kanes (7a-e) were prepared and evaluated for activity in the two-lever drug discrimination paradigm in rats trained...

DOI: 10.1021/jm960199j Mescaline Serotonin Hallucinogen Ketanserin +11

Effect of a Chiral 4-Alkyl Substituent in Hallucinogenic Amphetamines

Journal of Medicinal Chemistry September 1, 1995 Robert Oberlender, P. V. Ramachandran, Michael P. Johnson et al. 8 citations

The potency of hallucinogenic amphetamine derivatives of the 1-(2,5-dimethoxy-4-alkylphenyl)-2-aminopropane type drops dramatically when the length of the 4-alkyl substituent exceeds propyl or when the substituent is branched. This investigation was directed toward evaluating changes in behavioral and biochemical pharmacology resulting from introducing chirality into the 4-alkyl group of such...

DOI: 10.1021/jm00018a019

Stereoselective LSD-like Activity in a Series of d-Lysergic Acid Amides of (R)- and (S)-2-Aminoalkanes

Journal of Medicinal Chemistry March 1, 1995 Aaron Monte, Danuta Marona‐lewicka, Arthi Kanthasamy et al. 25 citations

The 3-pentyl-, (R)- and (S)-2-pentyl-, 2-hexyl-, and 2-heptylamides of d-lysergic acid were synthesized and evaluated in biochemical and behavioral assays for LSD-like activity. In radioligand competition studies, the (R)-lysergamides were consistently more potent than the (S)-amides in displacing [3H]ketanserin from 5-HT2A receptors in rat cortical homogenate and in displacing [3H]-8-OH-DPAT...

DOI: 10.1021/jm00006a015 Lysergic acid diethylamide Stereochemistry Stereoselectivity Carboxamide +3

Stereoselective LSD-like activity in d-lysergic acid amides of R- and S-2-aminobutane

Journal of Medicinal Chemistry 1992 Robert Oberlender, Robert C. Pfaff, Michael P. Johnson et al. 17 citations

The (R)- and (S)-2-butylamides of d-lysergic acid were prepared and evaluated in behavioral and biochemical assays of 5-HT2 agonist activity. In rats trained to discriminate 0.08 mg/kg LSD tartrate from saline, both isomers completely substituted for the training stimulus. Similarly, both isomers were found to possess very high affinity in displacing [125I]-(R)-DOI...

DOI: 10.1021/jm00080a001 Lysergic acid diethylamide Stereochemistry Agonist Substituent +4

Synthesis and pharmacological examination of 1-(3-methoxy-4-methylphenyl)-2-aminopropane and 5-methoxy-6-methyl-2-aminoindan: similarities to 3,4-(methylenedioxy)methamphetamine (MDMA)

Journal of Medicinal Chemistry May 1, 1991 Michael P. Johnson, Stewart Frescas, Robert Oberlender et al. 53 citations

The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In...

DOI: 10.1021/jm00109a020 MDMA Methylenedioxy Methamphetamine Stereochemistry +2

2,3-Dihydrobenzofuran analogs of hallucinogenic phenethylamines

Journal of Medicinal Chemistry 1991 David E. Nichols, Scott E. Snyder, Robert Oberlender et al. 45 citations

Two 2,3-dihydrobenzofuran analogues of hallucinogenic amphetamines were prepared and evaluated for activity in the two-lever drug-discrimination paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg) and for the ability to displace [125I]-(R)-DOI [( 125I]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) from rat cortical homogenate 5-HT2 receptors. The compounds,...

DOI: 10.1021/jm00105a043 Phenethylamines Hallucinogen Pharmacology Stereochemistry +1

Nonneurotoxic tetralin and indan analogs of 3,4-(methylenedioxy)amphetamine (MDA)

Journal of Medicinal Chemistry February 1, 1990 David E. Nichols, William K. Brewster, Michael P. Johnson et al. 83 citations

Four cyclic analogues of the psychoactive phenethylamine derivative 3,4-(methylenedioxy)amphetamine were studied. These congeners, 5,6- and 4,5-(methylenedioxy)-2-aminoindan (3a and 4a, respectively), and 6,7- and 5,6-(methylenedioxy)-2-aminotetralin (3b and 4b, respectively) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Two groups of rats were trained...

DOI: 10.1021/jm00164a037 Citation Icon Information retrieval Library science

Synthesis and serotonin receptor affinities of a series of enantiomers of .alpha.-methyltryptamines: evidence for the binding conformation of tryptamines at serotonin 5-HT1B receptors

Journal of Medicinal Chemistry July 1, 1988 David Nichols, D. H. Lloyd, Michael P. Johnson et al. 46 citations

A procedure for the preparation of optically pure alpha-methyltryptamines (AMTs) from substituted indoles was developed. The key step in the sequence was the reductive amination of substituted indole-2-propanones with the commercially available pure enantiomers of alpha-methylbenzylamine, followed by the chromatographic separation of the resulting pair of diastereomeric amines by preparative...

DOI: 10.1021/jm00402a026 Serotonin Enantiomer Tryptamines Stereochemistry +5

Chemical and enzymatic oxidative coupling of 5-hydroxy-N,N-dimethyltryptamine with amines.

Journal of Medicinal Chemistry July 1, 1987 F Babin, T Huynh-Dinh 13 citations

As part of a program aiming to obtain a covalent labeling of serotoninergic receptors we have studied the oxidative coupling of serotonin derivatives with amino compounds. The oxidation of bufotenine (2) by MnO2 and human ceruloplasmin followed by the Michael type addition with dansylcadaverine and dansyllysine gave a fluorescent adduct identified as fused oxazole structure 4.

DOI: 10.1021/jm00390a020 Full text

Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class

Journal of Medicinal Chemistry October 1, 1986 David E. Nichols, Andrew J. Hoffman, Robert Oberlender et al. 189 citations

The alpha-ethyl phenethylamine derivative 1-(1,3-benzodioxol-5-yl)-2-butanamine was prepared. An asymmetric synthesis was used to prepare the enantiomers of this compound and the related alpha-methyl homologue (MDA). The racemates and enantiomers of both compounds were evaluated in the two-lever drug discrimination assay in rats trained to discriminate saline from 0.08 mg/kg of LSD tartrate....

DOI: 10.1021/jm00160a035 Enantiomer Phenethylamine Stereochemistry

Synthesis and evaluation of 2,3-dihydrobenzofuran analogs of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane: drug discrimination studies in rats

Journal of Medicinal Chemistry February 1, 1986 David E. Nichols, Andrew J. Hoffman, Robert Oberlender et al. 34 citations

Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats trained to discriminate saline from LSD tartrate (0.08 mg/kg), stimulus generalization occurred to both...

DOI: 10.1021/jm00152a022 Citation Icon Altmetrics Social media +2

Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives

Journal of Medicinal Chemistry September 1, 1985 Andrew J. Hoffman, David E. Nichols 44 citations

A convenient method for the synthesis of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives was developed. A series of these compounds was synthesized and tested for substitution in the two-lever drug discrimination assay, in rats trained to discriminate injections of d-LSD tartrate (185.5 nmol/kg, ip) from saline. A dose-response curve for each of the compounds in the series was...

DOI: 10.1021/jm00147a022 Lysergic acid diethylamide Alkyl Stimulus control Discriminative model +1

Synthesis and evaluation of substituted 2-phenylcyclobutylamines as analogs of hallucinogenic phenethylamines: lack of LSD-like biological activity

Journal of Medicinal Chemistry September 1, 1984 David E. Nichols, K. P. Jadhav, Robert Oberlender et al. 12 citations

cis- and trans-2-(2,4,5-trimethoxyphenyl)cyclobutylamine and trans-2-(2,5-dimethoxy-4-methylphenyl)cyclobutylamine were synthesized as conformationally restricted analogues of hallucinogenic phenylisopropylamines. In rats trained to discriminate saline from LSD (0.08 mg/kg, ip) in a two-lever drug discrimination paradigm, no generalization of the LSD stimulus to the cis trimethoxy compound...

DOI: 10.1021/jm00375a004 Mescaline Phenethylamines Hallucinogen Biological activity +2

Sulfur analogs of psychotomimetic agents. 30. Ethyl homologs of mescaline and their monothioanalogs

Journal of Medicinal Chemistry July 1, 1984 Peyton Jacob, Alexander T. Shulgin 14 citations

All possible monothio analogues of the mono-, di-, and triethoxy homologues of mescaline have been synthesized and pharmacologically evaluated in man. Modifications at the ring position para to the ethylamine chain, either with a sulfur atom, a longer alkyl chain, or both, lead to compounds of high central nervous system activity. The 4-n-propoxy and 4-n-butoxy homologues and their...

DOI: 10.1021/jm00373a013 Mescaline Psychotomimetic Citation Social media +3

Sulfur analogs of psychotomimetic agents. 2. Analogs of (2,5-dimethoxy-4-methylphenyl)- and of (2,5-dimethoxy-4-ethylphenyl)isopropylamine

Journal of Medicinal Chemistry May 1, 1983 Peyton Jacob, Alexander T. Shulgin 18 citations

The two thio analogues of each of the well-known psychotomimetic drugs DOM [(2,5-dimethoxy-4-methylphenyl)isopropylamine] and DOET [(2,5-dimethoxy-4-ethylphenyl)isopropylamine] have been synthesized and pharmacologically evaluated in man. The 5-thio isomers are more potent as psychotomimetic agents than the 2-thio isomers but still represent a drop of an order of magnitude in potency from the...

DOI: 10.1021/jm00359a021 Isopropylamine Psychotomimetic Thio- Tetrahydrothiophene +5

Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes

Journal of Medicinal Chemistry May 1, 1982 David E. Nichols, David Harley Lloyd, Andrew J. Hoffman et al. 178 citations

The enantiomers of 3,4-(methylenedioxy)amphetamine (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA (MDMA), along with their alpha, alpha-dimethylated derivatives, were evaluated for an effect on the release of [3H]serotonin from rat whole brain synaptosomes. The amphetamine isomers were all potent in inducing the release of [3H]serotonin at bath concentrations of 1 and 10 micrometers but were...

DOI: 10.1021/jm00347a010 MDMA Citation Amphetamine

Isomeric cyclopropyl ring-methylated homologs of trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine, an hallucinogen analog

Journal of Medicinal Chemistry May 1, 1982 James N. Jacob, David E. Nichols 6 citations

The hallucinogen analogue trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine was modified by adding a 3-methyl group, either cis or trans with respect to the amino group. These two isomeric cyclopropyl ring-methylated compounds were then tested for activity in the mouse ear-scratch assay and for a contractile effect in the rat fundus preparation. Neither compound was found to possess...

DOI: 10.1021/jm00347a009 Hallucinogen Stereochemistry Ring chemistry Pharmacology +2

Sulfur analogues of psychotomimetic agents. Monothio analogs of mescaline and isomescaline

Journal of Medicinal Chemistry November 1, 1981 Peyton Jacob, Alexander T. Shulgin 20 citations

Two monothio analogues of mescaline and three monothio analogues of 2,3,4-trimethoxyphenethylamine (isomescaline) have been synthesized and characterized. Only the two mescaline analogues (3-and 4-thiomescaline) were found to be psychotomimetics in man, being 6 and 12 times more potent than mescaline, respectively. All five compounds can serve as substrates for bovine plasma monoamine oxidase...

DOI: 10.1021/jm00143a017 Mescaline Psychotomimetic Pharmacology Hallucinogen

Comparison of solution conformational preferences for the hallucinogens bufotenin and psilocin using 360-MHz proton NMR spectroscopy.

Journal of Medicinal Chemistry February 1, 1981 G P Migliaccio, T L Shieh, S R Byrn et al. 34 citations

The 360-MHz 1H NMR spectra of bufotenin and psilocin were obtained, both as the free bases in CDCl3 and as protonated salts in D2O. Coupling constants for the side-chain methylenes were derived using the LAOCN3 program. These time-averaged coupling constants indicate that the trans and gauche rotamers of both compounds have about equal energy in D2O. There is a slight excess of the trans...

DOI: 10.1021/jm00134a016 Full text

Studies on several 7-substituted N,N-dimethyltryptamines

Journal of Medicinal Chemistry November 1, 1980 Richard A Glennon, E. Schubert, John M. Jacyno et al. 33 citations

Several 7-substituted derivatives of N,N-dimethyltryptamine (DMT) were prepared and evaluated in the rat fundus serotonin receptor assay and in a behavioral (discriminative stimulus) assay in rats. Both 7-Me- and 5-OMe-7-Me-DMT possess a higher pA2, and 5,7-(OMe)2-DMT a lower pA2, than that of DMT itself. Like DMT, all three of these compounds produce behavioral effects in rats which are...

DOI: 10.1021/jm00185a014 Stereochemistry

Phenylalkylamines with potential psychotherapeutic utility. 2. Nuclear substituted 2-amino-1-phenylbutanes

Journal of Medicinal Chemistry February 1, 1980 Robert T. Standridge, Henry G. Howell, Hugh A. Tilson et al. 13 citations

A series of 2-amino-1-(4-substituted-2,5-dimethoxyphenyl)butanes (Table V) was prepared as analogues of (R)-2-amino-1-(2,5-dimethoxy-4-methylphenyl)butane (1a). 1-(2,5-Dimethoxyphenyl)-2-(N-phthalimido)butane (7) was utilized as a synthetic intermediate common to many of the target compounds. Animal data are presented indicating that most of these analogues have low hallucinogenic potential....

DOI: 10.1021/jm00176a010 Hallucinogen Butane Stereochemistry Chemical synthesis +2

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